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- Helbig, K. L., et al.
(författare)
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De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias
- 2018
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 103:5, s. 666-678
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Tidskriftsartikel (refereegranskat)abstract
- Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the alpha(1)-subunit of the voltage-gated Ca(V)2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed Ca(V)2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.
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| 5. |
- Boysen, Lena R., et al.
(författare)
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Global climate response to idealized deforestation in CMIP6 models
- 2020
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4189. ; 17, s. 5615-5638
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Tidskriftsartikel (refereegranskat)abstract
- Changes in forest cover have a strong effect on climate through the alteration of surface biogeophysical and biogeochemical properties that affect energy, water and carbon exchange with the atmosphere. To quantify biogeophysical and biogeochemical effects of deforestation in a consistent setup, nine Earth system models (ESMs) carried out an idealized experiment in the framework of the Coupled Model Intercomparison Project, phase 6 (CMIP6). Starting from their pre-industrial state, models linearly replace 20×106 km2 of forest area in densely forested regions with grasslands over a period of 50 years followed by a stabilization period of 30 years. Most of the deforested area is in the tropics, with a secondary peak in the boreal region. The effect on global annual near-surface temperature ranges from no significant change to a cooling by 0.55 ∘C, with a multi-model mean of −0.22±0.21 ∘C. Five models simulate a temperature increase over deforested land in the tropics and a cooling over deforested boreal land. In these models, the latitude at which the temperature response changes sign ranges from 11 to 43∘ N, with a multi-model mean of 23∘ N. A multi-ensemble analysis reveals that the detection of near-surface temperature changes even under such a strong deforestation scenario may take decades and thus longer than current policy horizons. The observed changes emerge first in the centre of deforestation in tropical regions and propagate edges, indicating the influence of non-local effects. The biogeochemical effect of deforestation are land carbon losses of 259±80 PgC that emerge already within the first decade. Based on the transient climate response to cumulative emissions (TCRE) this would yield a warming by 0.46 ± 0.22 ∘C, suggesting a net warming effect of deforestation. Lastly, this study introduces the “forest sensitivity” (as a measure of climate or carbon change per fraction or area of deforestation), which has the potential to provide lookup tables for deforestation–climate emulators in the absence of strong non-local climate feedbacks. While there is general agreement across models in their response to deforestation in terms of change in global temperatures and land carbon pools, the underlying changes in energy and carbon fluxes diverge substantially across models and geographical regions. Future analyses of the global deforestation experiments could further explore the effect on changes in seasonality of the climate response as well as large-scale circulation changes to advance our understanding and quantification of deforestation effects in the ESM frameworks.
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- Hammerlid, E, et al.
(författare)
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A prospective multicentre study in Sweden and Norway of mental distress and psychiatric morbidity in head and neck cancer patients
- 1999
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 80:5-6, s. 766-774
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Tidskriftsartikel (refereegranskat)abstract
- A Swedish/Norwegian head and neck cancer study was designed to assess prospectively the levels of mental distress and psychiatric morbidity in a heterogeneous sample of newly diagnosed head and neck cancer patients. A total of 357 patients were included. The mean age was 63 years, and 72% were males. The patients were asked to answer the HAD scale (the Hospital Anxiety and Depression scale) six times during 1 year. The number of possible or probable cases of anxiety or depression disorder was calculated according to standardized cut-offs. Approximately one-third of the patients scored as a possible or probable case of a major mood disorder at each measurement point during the study year. There were new cases of anxiety or depression at each time point. The anxiety level was highest at diagnosis, while depression was most common during treatment. Females were more anxious than males at diagnosis, and patients under 65 years of age scored higher than those over 65. Patients with lower performance status and more advanced disease reported higher levels of mental distress and more often scored as a probable or possible cases of psychiatric disorder. Our psychometric analyses supported the two-dimensional structure and stability of the HAD scale. The HAD scale seems to be the method of choice for getting valid information about the probability of mood disorder in head and neck cancer populations. The prevalence of psychiatric morbidity found in this study emphasizes the importance of improved diagnosis and treatment.
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| 7. |
- Hammerlid, Eva, 1957, et al.
(författare)
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A prospective study of quality of life in head and neck cancer patients. Part I: At diagnosis
- 2001
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Ingår i: Laryngoscope. - : Wiley. - 0023-852X. ; 111:4 Pt 1, s. 669-680
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: A Swedish and Norwegian study was designed to examine health-related quality of life (HQL) in patients with head and neck cancer (head and neck) at diagnosis and during treatment and rehabilitation. The overall aim was to examine the impact on HQL at diagnosis depending on tumor location, stage, sex, and age (part I) and to describe HQL longitudinally and determine for which patients and during which period HQL deteriorated most (part II), This article presents the results at diagnosis. Method Patients with head and neck cancer at five hospitals in Sweden and Norway were consecutively requested to participate, They were asked to answer the EORTC QLQ-C30 and QLQ-H&N35 (the European Organization for Research and Treatment of Cancer, Core 30 questionnaire and head and neck cancer module) repeatedly during I year. A total of 357 patients (mean age, 63 y; 72% males) were included, Results: Patients with different tumor locations all had their special problems at diagnosis, for example, those with tumors in the larynx with communication, those with oral tumors with pain, and those with pharyngeal tumors with nutrition and pain. The patients with hypopharyngeal cancer reported the worst HQL. Stage appeared to have the strongest impact on HQL. Patients with a more advanced tumor stage reported significantly worse HQL scores for 24 of 32 variables reflecting functioning or problems. The females scored worse than the males for some areas, in particular, emotional functioning. The older patients scored significantly better for emotional and social functioning than patients <65 years but worse for physical functioning and various symptoms. The traditional way of grouping the tumor locations into oral, pharyngeal, laryngeal, and "other" tumors (salivary gland, sinus and nose, and unknown primary) was tested from a HQL point of view and found to be consistent. Conclusions: The chosen questionnaires differentiated between different sites of head and neck cancer at diagnosis. Tumor stage had the most powerful impact on HQL score.
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- Magnusson, Carl, 1976, et al.
(författare)
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Suboptimal prehospital decision- making for referral to alternative levels of care - frequency, measurement, acceptance rate and room for improvement
- 2022
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Ingår i: Bmc Emergency Medicine. - : Springer Science and Business Media LLC. - 1471-227X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The emergency medical services (EMS) have undergone dramatic changes during the past few decades. Increased utilisation, changes in care-seeking behaviour and competence among EMS clinicians have given rise to a shift in EMS strategies in many countries. From transport to the emergency department to at the scene deciding on the most appropriate level of care and mode of transport. Among the non-conveyed patients some may suffer from "time-sensitive conditions" delaying diagnosis and treatment. Thus, four questions arise: How often are time-sensitive cases referred to primary care or self-care advice? How can we measure and define the level of inappropriate clinical decision-making? What is acceptable? How to increase patient safety? Main text To what extent time-sensitive cases are non-conveyed varies. About 5-25% of referred patients visit the emergency department within 72 hours, 5% are hospitalised, 1-3% are reported to have a time-sensitive condition and seven-day mortality rates range from 0.3 to 6%. The level of inappropriate clinical decision-making can be measured using surrogate measures such as emergency department attendances, hospitalisation and short-term mortality. These measures do not reveal time-sensitive conditions. Defining a scoring system may be one alternative, where misclassifications of time-sensitive cases are rated based on how severely they affected patient outcome. In terms of what is acceptable there is no general agreement. Although a zero-vision approach does not seem to be realistic unless under-triage is split into different levels of severity with zero-vision in the most severe categories. There are several ways to reduce the risk of misclassifications. Implementation of support systems for decision-making using machine learning to improve the initial assessment is one approach. Using a trigger tool to identify adverse events is another. Conclusion A substantial number of patients are non-conveyed, including a small portion with time-sensitive conditions. This poses a threat to patient safety. No general agreement on how to define and measure the extent of such EMS referrals and no agreement of what is acceptable exists, but we conclude an overall zero-vision is not realistic. Developing specific tools supporting decision making regarding EMS referral may be one way to reduce misclassification rates.
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| 10. |
- Bjordal, K, et al.
(författare)
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- 1999
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 17:3, s. 1008-1019
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to define the scales and test the validity, reliability, and sensitivity of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-H&N35, a questionnaire designed to assess the quality of life of head and neck (H&N) cancer patients in conjunction with the general cancer-specific EORTC QLQ-C30. PATIENTS AND METHODS: Questionnaires were given to 500 H&N cancer patients from Norway, Sweden, and the Netherlands as part of two prospective studies. The patients completed the questionnaires before, during (Norway and Sweden only), and after treatment, yielding a total of 2070 completed questionnaires. RESULTS: The compliance rate was high, and the questionnaires were well accepted by the patients. Seven scales were constructed (pain, swallowing, senses, speech, social eating, social contact, sexuality). Scales and single items were sensitive to differences between patient subgroups with relation to site, stage, or performance status. Most scales and single items were sensitive to changes, with differences of various magnitudes according to the site in question. The internal consistency, as assessed by Cronbach's alpha coefficient, varied according to assessment point and within subsamples of patients. A low overall alpha value was found for the speech and the senses scales, but values were higher in assessments of patients with laryngeal cancer and in patients with nose, sinus, and salivary gland tumors. Scales and single items in the QLQ-H&N35 seem to be more sensitive to differences between groups and changes over time than do the scales and single items in the core questionnaire. CONCLUSION: The QLQ-H&N35, in conjunction with the QLQ-C30, provides a valuable tool for the assessment of health-related quality of life in clinical studies of H&N cancer patients before, during, and after treatment with radiotherapy, surgery, or chemotherapy.
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